Beneficial effects of isometric strength training on endothelial dysfunction in rats

2006 ◽  
Vol 31 (5) ◽  
pp. 621-630 ◽  
Author(s):  
Hélène Figard ◽  
Vincent Gaume ◽  
Fabienne Mougin ◽  
Céline Demougeot ◽  
Alain Berthelot
Keyword(s):  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Isometric Exercise ◽  
Ovariectomized Rats ◽  
Daily Injection ◽  
Sprague Dawley ◽  
Estradiol Treatment ◽  
Sedentary Group ◽  
Age Related ◽  
17Β Estradiol

Using female 4-week-old Sprague–Dawley rats, we investigated the effects of 14 weeks of progressive strength isometric training on endothelium dysfunction after estrogen deficiency. We also proposed possible mechanism(s) by which such training acted on endothelium-dependent vasodilation in thoracic aortic rings. Rats were randomly divided into 4 groups of 8 rats: a sham operated group, an ovariectomized sedentary group receiving 17β-estradiol vehicle s.c. daily, an ovariectomized sedentary group receiving a daily injection of 20 µg·kg–1 17β-estradiol s.c., and an ovariectomized exercised group receiving daily s.c. vehicle. Vascular reactivity of aortic rings have been evaluated by a cumulative dose of acetylcholine (ACh), in the presence or absence of l-NAME (N-nitro-l-arginine methyl ester), indomethacin, thapsigargin, iberiotoxin, apamin, and tetraethylammonium. Ovariectomy markedly decreased the relaxation caused by ACh, whereas 17β-estradiol treatment induced a significant increase in the relaxation elicited by ACh. Isometric exercise enhanced relaxation due to ACh. This enhancement was attenuated in the presence of l-NAME, indomethacin, thapsigargin, iberiotoxin, and apamin. Our data indicated, for the first time, that the endothelium-dependent relaxant response to ACh was markedly improved in trained ovariectomized rats. This increased vasodilation is mediated by nitric oxide, cyclooxygenase, sarco-endoplasmic reticulum Ca2+-ATPase pathways, and endothelium-derived hyperpolarizing factor. Finally, this study suggested that resistance training may provide benefits in addressing vascular dysfunction consequent to a decline in estrogen levels after menopause. However, any benefits for age-related vascular dysfunction remain to be demonstrated.

Coronary vascular reactivity is improved by endothelin A receptor blockade in DOCA-salt hypertensive rats

1998 ◽  
Vol 274 (6) ◽  
pp. R1613-R1618 ◽  
Author(s):  
Ararat D. Giulumian ◽  
David M. Pollock ◽  
Natalie Clarke ◽  
Leslie C. Fuchs
Keyword(s):  
Vascular Reactivity ◽  
Chronic Treatment ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Intraluminal Pressure ◽  
Receptor Blockade ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Salt Hypertension

Endothelin-1 (ET-1) is thought to play an important role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Because hypertension is associated with an increased incidence of coronary artery disease, this study was designed to determine if coronary vascular contraction to ET-1 is altered in DOCA-salt hypertensive rats and to determine the effect of chronic treatment of DOCA-salt rats with the selective ETA receptor antagonist A-127722. Male Sprague-Dawley rats were divided into four groups: DOCA, Placebo, DOCA + A-127722, and Placebo + A-127722. A-127722 was administered in drinking water at a concentration of 8 mg/100 ml. After 3 wk, mean arterial pressure (MAP) was significantly enhanced in DOCA-salt compared with Placebo rats. A-127722 significantly inhibited the increase in MAP. Contraction to ET-1 (10−11 to 3 × 10−8 M) was measured in isolated coronary and mesenteric small arteries (200–300 μm, intraluminal diameter) maintained at a constant intraluminal pressure of 40 mmHg and was significantly impaired in vessels from DOCA-salt compared with Placebo rats. Dose-dependent contractions to KCl were also inhibited in coronary, but only minimally impaired in mesenteric, arteries of DOCA-salt rats. Inhibition of nitric oxide synthase activity did not restore contraction to ET-1 in coronary small arteries. However contractions to ET-1 were enhanced in mesenteric small arteries. Chronic treatment with A-127722 significantly restored contraction to ET-1 in coronary, but not in mesenteric, arteries of DOCA-salt rats. Because ETAreceptor blockade impairs the development of hypertension and improves coronary vascular reactivity, these data indicate that ET-1 plays an important role in coronary vascular dysfunction associated with DOCA-salt hypertension.

Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake

2002 ◽  
Vol 282 (5) ◽  
pp. E1139-E1146 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Glucose Uptake ◽  
Glycogen Content ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Transporter Protein ◽  
Glut4 Expression ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

This study examined the roles of the female sex steroids, 17β-estradiol (E2) and progesterone (Prog), on glucose uptake and GLUT4 protein expression. Female Sprague-Dawley rats were either sham operated (C) or ovariectomized and treated with placebo (O), E2 (E), Prog (P), or both hormones at physiological doses (P + E) or the same dose of Prog with a high dose of E2 (P + HiE) via timed-release pellets inserted at the time of surgery, 15 days before metabolic testing. On the morning of day 15, animals received a 300-μCi injection (ip) of 2-deoxy-[14C]glucose and then either exercised on a motorized treadmill for 30 min at 0.35 m/s or remained sedentary in their cages for the same period. Basal glucose uptake was not different between the treatment groups in either the red or white quadriceps. However, glucose uptake was decreased ( P < 0.05) in O, P, and P + E rats during exercise in the red quadriceps compared with C rats, whereas E and P + HiE treatment restored glucose uptake. Glycogen content in skeletal muscle followed similar trends, with no differences seen in resting animals. Postexercise red quadriceps glycogen levels were higher ( P < 0.05) in the E and P + HiE rats compared with O and P. Treatment of ovariectomized rats with progesterone (P rats) decreased ( P < 0.05) GLUT4 content in the red quadriceps by 21% compared with C rats. These data demonstrate that estrogen-deficient animals have a decreased ability for contraction-stimulated glucose uptake and increased glycogen use during aerobic exercise. However, changes in contraction-stimulated glucose uptake could not be explained by altered transporter protein content, since the absence of E2 had no effect on GLUT4 protein.

Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscle

2001 ◽  
Vol 281 (4) ◽  
pp. E803-E808 ◽  
Author(s):  
S. E. Campbell ◽  
M. A. Febbraio
Keyword(s):  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Maximal Activity ◽  
Ovariectomized Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Muscle Enzyme ◽  
Sprague Dawley Rats ◽  
Oxidative Pathway ◽  
17Β Estradiol

To examine the roles of 17β-estradiol (E2) and progesterone (Prog) in lipid metabolism, skeletal muscle enzyme activities were studied in female Sprague-Dawley rats. Groups included sham-operated rats (C) and ovariectomized rats treated with placebo (O), E2 (E), Prog (P), both hormones at physiological doses (P + E), or both hormones with a high dose of E2 (P + HiE). Hormone (or vehicle only) delivery was via time-release pellets inserted at the time of surgery, 15 days before metabolic testing. Results demonstrated that carnitine palmitoyltransferase maximal activity was 19, 21, and 19% lower ( P < 0.01) in O, P, and P + E rats, respectively, compared with C rats. Conversely, activity in E and P + HiE rats was 14 and 19% higher ( P < 0.01) than in C. β-Hydroxyacyl-CoA dehydrogenase (β-HAD) maximal activity was 20% lower ( P < 0.01) in O than in C rats; similarly, P and P + E rats were 18 and 19% lower, respectively ( P < 0.01); however, treatment with E2returned β-HAD activity to C levels. These results suggest that E2 plays a role in lipid metabolism by increasing the maximal activity of key enzymes in the fat oxidative pathway of skeletal muscle.

Estrogen replacement increases coronary artery distensibility in ovariectomized rats

1999 ◽  
Vol 77 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Yunlong Zhang ◽  
Sandra T Davidge
Keyword(s):  
Wall Thickness ◽  
Vascular Remodeling ◽  
Mesenteric Arteries ◽  
Ovariectomized Rats ◽  
Estrogen Replacement ◽  
Sprague Dawley ◽  
Dual Chamber ◽  
Arterial Distensibility ◽  
Sprague Dawley Rats ◽  
17Β Estradiol

The effect of estrogen on the passive characteristics of arteries is not known. We hypothesized that estrogen would increase arterial distensibility as part of its protective effect on the vasculature. Female Sprague-Dawley rats were ovariectomized at 11 weeks of age. One group received a placebo (n = 6), while two other groups (n = 5 each) of rats received a 17β-estradiol pellet (0.15 mg or 0.5 mg with 60-day release). After 4 weeks of estrogen replacement, coronary and mesenteric arteries (<200 µm diameter) were dissected and mounted on a dual-chamber arteriograph. Lumen diameter and wall thickness were measured in pressurized arteries. The relative changes in diameter (distensibility) as well as wall thickness per unit change in pressure were significantly increased (p < 0.05) in the coronary arteries of the 0.5 mg estradiol replaced rats compared with the ovariectomized control animals and the 0.15 mg estradiol replaced rats. Surprisingly, in the mesenteric arteries from the same animals, there was no difference in distensibility or pressure - wall thickness among the groups. This study provides experimental data of a novel hypothesis that estrogen may afford part of its protection through vascular remodeling of the coronary circulation.Key words: vasculature, remodeling, cardiovascular disease.

The effect of 17β-estradiol treatment on the mass and the turnover of bone in ovariectomized rats taking a mild dose of thyroxin

1994 ◽  
Vol 24 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Motonori Yamaura ◽  
Toshitaka Nakamura ◽  
Azusa Kanou ◽  
Tomoshi Miura ◽  
Hiroyuki Ohara ◽  
...  
Keyword(s):  
Ovariectomized Rats ◽  
Estradiol Treatment ◽  
17Β Estradiol

17β-Estradiol reduces vasoconstriction in endothelium-denuded rat aortas through inducible NOS

1998 ◽  
Vol 274 (3) ◽  
pp. H853-H859 ◽  
Author(s):  
J. Binko ◽  
H. Majewski
Keyword(s):  
Nitric Oxide ◽  
Estrogen Therapy ◽  
Ovariectomized Rats ◽  
Protein Synthesis Inhibitor ◽  
Nitric Oxide Production ◽  
Estradiol Treatment ◽  
Oxide Production ◽  
17Β Estradiol ◽  
Inducible Nos

Estrogen produces vasodilatation through the induction of nitric oxide synthase (NOS) in the endothelium, but there are many reports of endothelium-independent effects. In the present study, these processes were investigated in rat aortas isolated from ovariectomized rats. Long-term in vitro treatment with 17β-estradiol (10 nM for 24 h) in an organ culture system slightly reduced acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings. 17β-Estradiol (1 and 10 nM for 24 h) also attenuated the phenylephrine-induced constriction in endothelium-denuded aortas, and this effect was inhibited by the NOS inhibitorl- N 5-(1-iminoethyl)ornithine hydrochloride, as well as the estrogen receptor antagonist ICI-182,780. Furthermore, 17β-estradiol treatment (1 and 10 nM for 24 h) increased nitric oxide production as assessed by the conversion of [3H]arginine to [3H]citrulline in endothelium-denuded rat aortas. These effects were prevented by the protein synthesis inhibitor cycloheximide. 17β-Estradiol (10 nM for 24 h) treatment also induced the formation of inducible NOS (iNOS) protein in aortas. The results indicate that 17β-estradiol can attenuate the vasoconstrictor effect of phenylephrine by a process that involves induction of iNOS in nonendothelial cells of the aorta. We suggest that long-term estrogen therapy may induce a partial hyporesponsiveness in vascular smooth muscle via a small but sustained nitric oxide production.

scholarly journals Estradiol Protects against Ischemic Injury

1998 ◽  
Vol 18 (11) ◽  
pp. 1253-1258 ◽  
Author(s):  
Dena B. Dubal ◽  
Michael L. Kashon ◽  
L. Creed Pettigrew ◽  
Jing M. Ren ◽  
Seth P. Finklestein ◽  
...  
Keyword(s):  
Infarct Volume ◽  
Ischemic Injury ◽  
In Vivo Model ◽  
Sprague Dawley ◽  
Estradiol Treatment ◽  
Doppler Flowmetry ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Estradiol Levels

Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke, This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17β-estradiol levels in serum (10 or 60 pg/mL, respectively), One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean ± SD: oil = 241 ± 88; low = 139 ± 91; high = 132 ±88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.

scholarly journals Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 761 ◽  
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Aytan Musayeva ◽  
Adrian Gericke
Keyword(s):  
Intracellular Signaling ◽  
Vascular Reactivity ◽  
Vascular System ◽  
Vascular Dysfunction ◽  
Special Focus ◽  
Retinal Diseases ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Pathophysiological Role ◽  
Neuron Function

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.

17β-Estradiol deficiency reduces potassium excretion in an angiotensin type 1 receptor-dependent manner

2007 ◽  
Vol 293 (1) ◽  
pp. H17-H22 ◽  
Author(s):  
Hong Ji ◽  
Wei Zheng ◽  
Celine Falconetti ◽  
Darren M. Roesch ◽  
Susan E. Mulroney ◽  
...  
Keyword(s):  
Renal Function ◽  
Enzyme Inhibitor ◽  
Binding Capacity ◽  
Fractional Excretion ◽  
Ovariectomized Rats ◽  
Dependent Manner ◽  
Potassium Excretion ◽  
Sprague Dawley ◽  
17Β Estradiol

This study examined the effects of ovariectomy (OVX) and 17β-estradiol (E2) replacement (OVX + E2) on renal function in Sprague-Dawley rats. OVX caused a 40% decrease in the fractional excretion of potassium (FEK+) that was prevented by E2 replacement [Sham, 24.2 ± 2.9%; OVX, 14.5 ± 2.1% ( P < 0.05 vs. OVX + E2); and OVX + E2, 26.2 ± 2.7%; n = 7–11] and that corresponded to significant increases in plasma potassium [(in mmol/l): Sham, 3.15 ± 0.087; OVX, 3.42 ± 0.048 ( P < 0.05 vs. OVX + E2); and OVX + E2, 3.19 ± 0.11; n = 7–11]. No effects of OVX were detected on plasma levels of sodium and aldosterone. Angiotensin II type 1 receptor (AT1R) densities in ovariectomized rats were 1.4-fold and 1.3-fold higher in glomerular [maximum binding capacity (Bmax; in fmol/mg protein): Sham, 482 ± 21; OVX, 666 ± 20 ( P < 0.05 vs. OVX + E2); and OVX + E2, 504 ± 26; n = 7–11] and proximal tubular [Bmax (in fmol/mg protein): Sham, 721 ± 16; OVX, 741 ± 24 ( P < 0.05 vs. OVX + E2); and OVX + E2, 569 ± 23; n = 7–11] membranes compared with E2 replete animals, respectively. Both the angiotensin-converting enzyme inhibitor captopril and the AT1R antagonist losartan prevented the OVX-induced decrease in the FEK+ and the increase in renal AT1R densities, suggesting that E2 deficiency reduces potassium excretion in an ANG II/AT1R-dependent manner. These findings may have implications for renal function in postmenopausal women as well as contribute to the reasons underlying the age-induced increase in susceptibility to hypertension-associated disease in women.

scholarly journals Relaxin and Castration in Male Mice Protect from, but Testosterone Exacerbates, Age-Related Cardiac and Renal Fibrosis, Whereas Estrogens Are an Independent Determinant of Organ Size

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 188-199 ◽  
Author(s):  
Tim D. Hewitson ◽  
Chongxin Zhao ◽  
Belinda Wigg ◽  
Sin Wai Lee ◽  
Evan R. Simpson ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Gene Knockout ◽  
Hormone Replacement ◽  
Weight Ratio ◽  
Organ Size ◽  
Wild Type ◽  
Estradiol Treatment ◽  
Collagen Concentration ◽  
Age Related ◽  
17Β Estradiol

This study determined the effects of castration and hormone replacement therapy on the age-related cardiac and renal pathology of male relaxin gene-knockout (RlnKO) and age-matched wild-type (RlnWT) mice and that of aged male aromatase knockout (ArKO) mice, which lack estrogens and have 5–10 times the androgen levels of male wild-type mice. One-month-old RlnWT and RlnKO mice were bilaterally gonadectomized or sham operated and maintained until 12 months. Subgroups of castrated animals received testosterone or 17β-estradiol treatment from 9 to 12 months. Male ArKO mice and aromatase wild-type mice were aged to 12 months. Collected heart and kidney tissues were assessed for changes in organ size and fibrosis. Castration reduced body, heart, left ventricle, and kidney weights in both RlnKO and RlnWT mice, and the cardiac/renal fibrosis that was seen in sham RlnKO animals (all P &lt; 0.05 vs. respective sham). Testosterone normalized organ weights and organ weight to body weight ratio of castrated animals and increased cardiac/renal collagen concentration to levels measured in or beyond that of sham RlnKO mice (all P &lt; 0.05 vs. respective castrated mice). Furthermore, expression of TGF-β1, mothers against decapentaplegic homolog 2 (Smad2), and myofibroblast differentiation paralleled the above changes (all P &lt; 0.05 vs. respective castrated mice), whereas matrix metalloproteinase-13 was decreased in testosterone-treated RlnKO mice. Conversely, 17β-estradiol only restored changes in organ size. Consistent with these findings, intact ArKO mice demonstrated increased cardiac/renal fibrosis in the absence of changes in organ size. These findings suggest that relaxin and castration protect, whereas androgens exacerbate, cardiac and renal fibrosis during ageing, whereas estrogens, in synergy with relaxin, regulates age-related changes in organ size.

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